The co-occurrence of chronic hepatitis C virus (HCV) infection, drug dependence and psychiatric disorders is one of the greatest public health challenges to the incarcerated population. HCV itself can cause psychiatric impairment, and drug use and psychiatric symptoms are leading causes of denial or discontinuation of pegylated interferon (peglFN) plus ribavirin (RBV) therapy. Colleagues and we have shown that in-prison HCV treatment is safe and effective for inmates serving long sentences, but most inmates are incarcerated for less than one year. An integrated model of behavioral health and HCV treatment that bridges the transition from prison to community is thus needed to facilitate the stabilization and treatment of the large proportion of HCV-infected inmates at high risk for psychiatric side effects from peg-IFN/RBV. This study will thus adapt and pilot test a continuity of care model between the prison and community settings for inmates infected with HCV genotype 1 or 4 who have a history of drug use; lifetime mood or anxiety disorder by DSM-IV criteria or current depressive/anxiety symptoms, and have 6 to 15 months remaining in their sentences. In a six-month "run-in" phase, 56 inmates would be assessed then initiate substance abuse, mental health and HCV treatment while in prison. Those who have a 12-week early virologic response without decompensation in prison (N=45) would be 2:1 randomized in the community treatment phase. Intervention subjects (N=30) would receive detailed transitional discharge planning, intensive therapeutic case management and linkage to addiction, mental health, benefits, and social services, life skills training and accompanied HCV clinic visits for up to 9 months. Comparison subjects (N=15) would receive a brief motivational intervention to enhance their commitment to continued treatment, usual discharge planning and referral from existing case management agencies. Both groups would receive weekly-supervised peglFN, an HCV support group and psychiatric care from the study provider. Primary outcomes will be HCV treatment completion and antiviral treatment discontinuation related to drug use or depressive/anxiety symptoms. Secondary outcomes are illicit drug use, recidivism, level of depressive/anxiety symptoms, and rates of end-of-treatment virologic response. For HCV-infected inmates, prison provides a controlled environment in which to stabilize substance use and mental health, and assess tolerability of and response to peglFN/RBV. This proposed reentry program would facilitate stabilization and treatment of the majority of inmates at risk for discontinuation of peglFN/RBV. Results would allow sample size estimation for a larger CJ-DATS multisite trial. If safety and efficacy can be established, a large number of inmates with HCV, who are not currently candidates for peg-IFN/RBV, could gain access to needed antiviral treatment. Such increased access to therapy would benefit public health and public safety. [unreadable] [unreadable] [unreadable]